Amiodarone Treatment for Symptomatic Atrial Fibrillation
Direct Recommendation
Amiodarone is highly effective for maintaining sinus rhythm in AF patients with structural heart disease, heart failure, or coronary artery disease, but should be reserved as second-line therapy in patients without structural heart disease due to significant long-term toxicity risks. 1
Treatment Strategy Based on Clinical Context
For Rate Control in Acute Settings
Intravenous amiodarone (150 mg over 10 minutes, then 0.5-1 mg/min infusion) is recommended for rate control when other measures fail or are contraindicated, particularly in patients with heart failure and AF without an accessory pathway. 2
IV amiodarone can be useful when beta blockers or calcium channel blockers are unsuccessful or contraindicated (Class IIa recommendation). 2
For patients with AF and rapid ventricular response causing hemodynamic compromise, IV amiodarone is appropriate for acute rate control. 2
For Chronic Rate Control
Oral amiodarone (200 mg daily maintenance) may be considered when ventricular rate cannot be adequately controlled at rest and during exercise with beta blockers, calcium channel blockers, or digoxin, alone or in combination (Class IIb recommendation). 2
This represents a lower-tier option for rate control, used only when first-line agents prove insufficient. 2
Rhythm Control Strategy: Patient Selection Algorithm
First-Line Candidates for Amiodarone
Amiodarone should be the initial antiarrhythmic choice in patients with: 1
- Heart failure with reduced ejection fraction (LVEF <40%)
- Severe left ventricular hypertrophy
- Coronary artery disease or prior myocardial infarction
- Structural heart disease where Class IC agents are contraindicated
Second-Line Use (After Other Agents Fail)
In patients without structural heart disease, try flecainide, propafenone, or sotalol first; reserve amiodarone for refractory cases. 2, 1
Dosing Regimens
For Rhythm Control/Cardioversion
Loading phase: 2
- 800 mg daily orally for 1 week
- 600 mg daily for 1 week
- 400 mg daily for 4-6 weeks
- 200 mg daily (or 100-200 mg daily using lowest effective dose)
- Some elderly patients can be maintained on 100 mg daily 3
Acute IV Cardioversion
- 150 mg IV over 10 minutes, followed by continuous infusion (900-3000 mg daily) 2
- Conversion is delayed compared to Class IC agents (effective at 6-8 hours and 24 hours, not at 1-2 hours) 2
Efficacy Data
Rhythm Maintenance
Amiodarone is the most effective antiarrhythmic for maintaining sinus rhythm, with 60-65% of patients remaining in sinus rhythm at one year versus 23-38% with other agents. 1
In the SAFE-T trial, conversion occurred in 27% of persistent AF patients after 28 days with amiodarone versus 24% with sotalol and 0.8% with placebo. 2
For paroxysmal AF with heart failure, amiodarone suppressed paroxysms in 88% of patients. 4
Heart Failure Patients
In AF patients with CHF and successful rhythm control, LVEF increased from 33±7% to 50±13% and BNP decreased from 723±566 to 248±252 pg/ml. 4
Patients with LVEF ≤30% benefited comparably to those with LVEF >30%. 4
Critical Safety Monitoring Requirements
Mandatory Baseline Assessment 1
Before initiating amiodarone, obtain:
- Chest radiograph
- Pulmonary function tests with DLCO
- Thyroid function tests (TSH, free T4)
- Liver enzymes (AST, ALT)
- ECG (assess QTc interval)
- Ophthalmologic examination
Ongoing Monitoring (Every 6 Months Minimum) 1
Repeat all baseline tests at least every 6 months during therapy.
Major Toxicities to Monitor 2, 5
Pulmonary toxicity:
- Occurs in 7-18% of patients 6
- Early-onset (days to weeks): pulmonary infiltrates, bronchospasm, wheezing, fever, dyspnea, hypoxia 5
- Late-onset: pulmonary fibrosis 5
- Can progress to ARDS or respiratory failure 5
Thyroid dysfunction:
- Both hypothyroidism and hyperthyroidism can occur 2, 5
- Amiodarone-induced thyrotoxicosis may cause arrhythmia breakthrough or death 5
- If new arrhythmias appear, consider hyperthyroidism 5
Ocular toxicity:
- Optic neuropathy/neuritis can cause permanent blindness 5
- Corneal deposits are common but usually asymptomatic 2
- Prompt ophthalmologic exam required for any visual changes 5
Hepatotoxicity:
- Monitor liver enzymes regularly 1
Cardiac effects:
- Bradycardia, heart block, QTc prolongation 2
- Torsade de pointes risk, especially with concomitant QT-prolonging drugs 5
Drug Interactions (Critical)
Anticoagulants 5
- Warfarin dose must be reduced by one-third to one-half when starting amiodarone, as prothrombin time increases by 100% after 3-4 days. 5
- Monitor INR closely to prevent serious or fatal bleeding 5
Digoxin 5
- Amiodarone increases serum digoxin by 70% after one day; reduce digoxin dose by approximately 50% or discontinue. 5
- Monitor levels and clinical toxicity 5
Other Antiarrhythmics 5
- Quinidine levels increase 33% after 2 days
- Procainamide and N-acetyl procainamide increase 55% and 33% respectively
- Reduce doses by one-third when co-administered 5
Beta Blockers and Calcium Channel Blockers 5
- Use with caution due to potentiation of bradycardia, sinus arrest, and AV block
- May require pacemaker insertion 5
Avoid Concomitant QTc-Prolonging Drugs 5
- Fluoroquinolones, macrolide antibiotics, azoles increase risk of torsade de pointes 5
Discontinuation Rates and Long-Term Sustainability
By 3 years, only 45% of patients remain on amiodarone therapy: 6
- 25% discontinue due to inefficacy
- 12% due to intolerance
- 18% due to toxicity
This challenges the notion of amiodarone as reasonable "destination" therapy for AF. 6
In another study, 23% of patients discontinued amiodarone due to complications during follow-up. 4
Comparison with Sotalol
Amiodarone is more effective than sotalol for maintaining sinus rhythm (relapse in 31/65 patients with amiodarone vs 47/61 with sotalol after average 6-8 months). 7
However, amiodarone causes significantly more side effects than sotalol. 7
Special Populations
Postoperative AF
- Preoperative amiodarone reduces incidence of AF after cardiac surgery (Class IIa recommendation). 2
Pregnancy
- Amiodarone use during pregnancy has been associated with congenital goiter/hypothyroidism and hyperthyroidism in neonates. 5
- Patients should be apprised of potential fetal hazards 5
Catheter Ablation as Alternative
In patients without structural heart disease who are candidates for both therapies, discuss catheter ablation as a first-line alternative to avoid long-term amiodarone toxicity. 1
Common Pitfalls to Avoid
Do not use amiodarone as first-line in structurally normal hearts – try flecainide, propafenone, or dronedarone first 1
Do not forget to reduce warfarin and digoxin doses when initiating amiodarone 5
Do not skip baseline and ongoing monitoring – toxicity is common and potentially fatal 1, 5
Do not combine with other QTc-prolonging drugs without careful risk assessment 5
Do not use IV calcium channel blockers or beta blockers in decompensated heart failure 2
Do not administer digoxin or calcium channel blockers to patients with accessory pathways – may paradoxically accelerate ventricular response 2
Avoid grapefruit juice – increases amiodarone levels by 50% (AUC) and 84% (Cmax) 5